The 2014 Gordon Research Conference on Mutagenesis, titled Changes to the Genetic Landscape, from Single Nucleotides to Entire Genomes, will focus on the causes and consequences of changes to the genetic landscape. The genomes of all organisms are constantly faced with environmental stress, particularly from exogenous sources. A primary challenge of this environmental stress to humans is the risk of mutagenesis and disease, including aging and age-related diseases such as cancer and neurodegeneration. Moreover, germ line mutations confer inherited diseases, including a wide range of rare diseases. There are positive aspects of mutagenesis as well, including its important contributions to immunology and evolution. Thus mutagenic processes, and their appropriate control, underlie many aspects of human health. The Mutagenesis conference is the premiere international venue for presenting new research on the underlying mechanisms and the health consequences of genetic changes. Recent findings by our speakers have revealed important new understanding of how mutagenesis stems from the success-or failure-of key cellular factors in facilitating DNA transactions. The conference will highlight new work encompassing a broad range of approaches, from mechanistic studies of mutagenesis, to the recent revolution in whole-genome analysis, to new therapeutic approaches. All these topics are covered by the 30 confirmed speakers from seven countries and representing academia, government and research institutes. An additional 8 speakers will be selected from submitted abstracts for talks interspersed in the schedule with the latest developments and to highlight new investigators. The schedule includes an opening keynote session, followed by daily morning and evening sessions entitled RNA-mediated mutagenesis; Genomic and chromosomal alterations; Challenges at the replication fork; Editing and repair; Decision points, repair or mutate; DNA polymerases and translesion synthesis; DNA structural challenges; and Targeted mutagenesis. The schedule also provides ample time for vibrant group discussions plus one-on-one and small group interactions. Daily poster sessions enable the presentation of additional work and facilitate direct interaction among students, postdoctoral fellows, new investigators, and more senior figures. Key objectives are to explore current knowledge at the frontier of mutagenesis research, with emphasis on molecular mechanisms and novel approaches to studying these mechanisms; to define therapeutic strategies to enhance the maintenance of genomic integrity and to take advantage of mutagenesis in the treatment of disease; to stimulate novel collaborations, especially exploiting work across experimental systems and disciplines; and to enhance and promote the careers of young scientists and encourage their continuation in the field. The new venue near Barcelona, Spain serves perfectly to further the Mutagenesis GRC tradition of alternating sites between Europe and the U.S. The site will provide full access and support to the conference, and is itself a significant attraction for potential attendees.